Abstract

Background

Cerebral malaria (CM) is a major cause of malaria mortality. Sequestration of infected
red blood cells and leukocytes in brain vessels coupled with the production of pro-inflammatory
factors contribute to CM. CXCL-10 a chemokine that is chemotactic to T cells has been
linked to fatal CM. Mice deficient for CXCL-10 gene are resistant to murine CM, while
antibody ablation of CXCL-10 enhanced the production of regulatory T cells (CD4+Cd25+Foxp3+)
and IL-10 which regulate the immune system. Interleukin-2 (IL-2), a pro-inflammatory
cytokine implicated in malaria pathogenesis has also been shown to be a key regulator
of Foxp3. However the role of Foxp3 in resistant murine CM is not well understood.

Methods

The hypothesis that resistance of CXCL-10-/- mice to murine CM may be due to enhanced
expression of Foxp3 in concert with IL-10 and IL-2 was tested. CXCL-10-/- and WT C57BL/6
mice were infected with Plasmodium berghei ANKA and evaluated for CM symptoms. Brain, peripheral blood mononuclear cells (PBMCs)
and plasma were harvested from infected and uninfected mice at days 2, 4 and 8. Regulatory
T cells (CD4+CD25+) and non-T regs (CD4+CD25-) were isolated from PBMCs and cultured
with P. berghei antigens in vitro with dendritic cells as antigen presenting cells. Regulatory T cell
transcription and specific factor Foxp3, was evaluated in mouse brain and PBMCs by
realtime-PCR and Western blots while IL-10, and IL-2 were evaluated in plasma and
cultured supernatants by ELISA.